Hydroxychloroquine Debate Rages in Federal Medicine

Hydroxychloroquine, which has been touted without definitive scientific support as a treatment for COVID-19 infection, has special significance for the millions of US military service members and veterans who served in Southwest Asia and other countries with endemic malaria: It’s a critical antimalarial drugs. It’s also needed for US Department of Veterans Affairs (VA) patients with rheumatoid arthritis.

On March 24, the VA Inspector General (IG) surveyed VA medical facilities to determine shortages in equipment as well as “antibiotics, sedatives, pain, and antiviral medications,” although there no known effective treatments for COVID-19. The OIG reported that 12 facilities indicated that they anticipated a shortage of medications, including hydroxychloroquine, lopinavir/ritonavir, IV immunoglobulin, and nebulizer products in the next 14 to 28 days. Facilities in West Haven, CT; Martinsburg, WV; Baltimore, MD; Washington, DC; Durham, NC; Columbia, SC; Tampa, FL; Detroit, MI; Temple, TX; Oklahoma City, OK; Aurora, CO; Seattle, WA; and Phoenix, AZ, all indicated anticipated shortages. At least one facility explicitly worried about access to medications and supplies produced in China and concern about disrupted supply chains may have concerned other facilities as well.

Nevertheless, hydroxychloroquine was at the top of mind both OIG inspectors as well as Veterans Health Administration (VHA) officials. In a formal response to the OIG survey, the VHA asserted: “We object to OIG’s assertions that a 14-day supply of chloroquine or hydroxychloroquine would have any merit. This is both inaccurate and irresponsible. There are active investigations into these drugs and many others, as discussed by Dr. Anthony Fauci. Yet no conclusions have been made on their effectiveness. To insist that a 14 days’ supply of these drugs is appropriate or not appropriate displays this dangerous lack of expertise on COVID-19 and Pandemic response.”

Hydroxychloroquine has been associated with serious adverse effects, such as cardiac arrhythmias and hypoglycemia, and its use against COVID-19 is based, so far, on thin evidence. It has shown promise in a laboratory setting against SARS-CoV-2, the virus that causes COVID-19, and in small studies with patients. Nonetheless, the Food and Drug Administration (FDA) has granted limited emergency authorization for certain uses of chloroquine and hydroxychloroquine against COVID-19. The rapid approval came apparently at the behest of the White House.

Former FDA leaders say the authorization has jeopardized research to learn the drugs’ real value in pandemic patients. They also charge that the decision undermines FDA’s scientific authority because it appears to be reacting to political advocacy. 

Despite the concerns, a run on chloroquine and hydroxychloroquine has been underway. According to a March 20 blog post by Premier, a hospital purchasing organization, orders for chloroquine and hydroxychloroquine jumped “dramatically” between March 1 and March 17, by 3,000% and 260%, respectively. Fortunately, these are older, relatively inexpensive oral drugs, Premier says, which means their manufacturing is “far less complicated” than for other drugs. To offer immediate help, Premier notes, drug makers such as Teva and Bayer have announced they will donate millions of tablets of the drugs to hospitals or the federal government for further testing.

Owing to “extraordinary public interest” in the off-label use of these drugs, numerous state boards of pharmacy have enacted emergency restrictions on the inappropriate dispensing of chloroquine and hydroxychloroquine, says the Quinism Foundation, a nonprofit organization that supports education and research on medical conditions caused by chloroquine and related drugs. And because of the very real potential for substitution of more dangerous quinolines (such as mefloquine) in place of chloroquine and hydroxychloroquine, the foundation recently called on state boards of pharmacy to enact uniform restrictions on the dispensing of all quinoline antimalarial drugs, with the understanding that any emergency use of any of these medications for public health purposes as attempted pandemic countermeasures would be best coordinated nationally through distribution from the Strategic National Stockpile.

In the meantime, research into hydroxychloroquine’s effectiveness is ongoing. “Coming at it from every angle”—that’s how Terry Welch, spokesman for the Walter Reed Army Institute of Research told Task & Purpose the Army is “leveraging specific competencies” to attack the COVID-19 problem. Among other things, WRAIR’s Emerging Infectious Diseases Branch (EIDB) is working to develop a vaccine against COVID-19 infection, including several versions of a novel vaccine candidate that has been tested in humans. WRAIR has also been conducting research into novel treatments, such as drug candidates similar to those successfully developed to treat malaria, and monoclonal antibodies.

WRAI was able to start its anti-COVID-19 research in early January—directly on the heels of the first reported cases of infection—because of the Institute’s history of researching related viruses. “If we hadn’t done that, we’d be weeks behind,” said Dr. Kayvon Modjarrad, director of EIDB.

The National Institutes of Health (NIH) has also begun a clinical trial, the Outcomes Related to COVID-19 treated with hydroxychloroquine among in-patients with symptomatic Diseases (ORCHID) study. The study will enroll more than 500 adults who are hospitalized with COVID-19 or in an emergency department awaiting hospitalization. All patients will continue to receive clinical care; some will be randomly assigned to also receive hydroxychloroquine. The first participants have been enrolled at Vanderbilt University Medical Center, in Nashville, one of the centers in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network.

In the “urgent race to find effective therapies,” NIH also launched the first clinical trial in the US to evaluate remdesivir, a broad-spectrum antiviral, as a potential treatment for COVID-19.  The trial, which started March 6 at the University of Nebraska Medical Center, is expected to conclude in May. Clinical trials of remdesivir have been ongoing in China, where the virus originated. The NIH study “takes into account” those trial designs. 

Many US hospitals are already using hydroxychloroquine as first-line therapy for COVID-19 patients, despite the lack of supportive clinical evidence. Wesley Self, MD, MPH, lead investigator in the ORCHID trial, says “[D]ata on hydroxychloroquine for the treatment of COVID-19 are urgently needed to inform clinical practice.”

Not only research is needed, but clear expression of the facts about the drugs. In March, shortly after the president began lauding hydroxychloroquine, a Phoenix man died of cardiac arrest and his wife ended up in critical care after they misguidedly ingested chloroquine phosphate, a chemical used to clean fish tanks.  “[W]e understand that people are trying to find new ways to prevent or treat this virus,” said Dr. Daniel Brooks, medical director of the Banner Poison and Drug Information Center in Phoenix, “but self-medicating is not the way to do so.”

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and one of the main spokespersons for science in the hydroxychloroquine debate, has continued to try to make his concerns clear: “I think we’ve got to be careful that we don’t make that majestic leap to assume this is a knockout drug,” he said in late March. “We still need to do the kinds of studies that definitively prove whether any intervention—not just this one, any intervention—is truly safe and effective.”

Hydroxychloroquine, which has been touted without definitive scientific support as a treatment for COVID-19 infection, has special significance for the millions of US military service members and veterans who served in Southwest Asia and other countries with endemic malaria: It’s a critical antimalarial drugs. It’s also needed for US Department of Veterans Affairs (VA) patients with rheumatoid arthritis.

On March 24, the VA Inspector General (IG) surveyed VA medical facilities to determine shortages in equipment as well as “antibiotics, sedatives, pain, and antiviral medications,” although there no known effective treatments for COVID-19. The OIG reported that 12 facilities indicated that they anticipated a shortage of medications, including hydroxychloroquine, lopinavir/ritonavir, IV immunoglobulin, and nebulizer products in the next 14 to 28 days. Facilities in West Haven, CT; Martinsburg, WV; Baltimore, MD; Washington, DC; Durham, NC; Columbia, SC; Tampa, FL; Detroit, MI; Temple, TX; Oklahoma City, OK; Aurora, CO; Seattle, WA; and Phoenix, AZ, all indicated anticipated shortages. At least one facility explicitly worried about access to medications and supplies produced in China and concern about disrupted supply chains may have concerned other facilities as well.

Nevertheless, hydroxychloroquine was at the top of mind both OIG inspectors as well as Veterans Health Administration (VHA) officials. In a formal response to the OIG survey, the VHA asserted: “We object to OIG’s assertions that a 14-day supply of chloroquine or hydroxychloroquine would have any merit. This is both inaccurate and irresponsible. There are active investigations into these drugs and many others, as discussed by Dr. Anthony Fauci. Yet no conclusions have been made on their effectiveness. To insist that a 14 days’ supply of these drugs is appropriate or not appropriate displays this dangerous lack of expertise on COVID-19 and Pandemic response.”

Hydroxychloroquine has been associated with serious adverse effects, such as cardiac arrhythmias and hypoglycemia, and its use against COVID-19 is based, so far, on thin evidence. It has shown promise in a laboratory setting against SARS-CoV-2, the virus that causes COVID-19, and in small studies with patients. Nonetheless, the Food and Drug Administration (FDA) has granted limited emergency authorization for certain uses of chloroquine and hydroxychloroquine against COVID-19. The rapid approval came apparently at the behest of the White House.

Former FDA leaders say the authorization has jeopardized research to learn the drugs’ real value in pandemic patients. They also charge that the decision undermines FDA’s scientific authority because it appears to be reacting to political advocacy. 

Despite the concerns, a run on chloroquine and hydroxychloroquine has been underway. According to a March 20 blog post by Premier, a hospital purchasing organization, orders for chloroquine and hydroxychloroquine jumped “dramatically” between March 1 and March 17, by 3,000% and 260%, respectively. Fortunately, these are older, relatively inexpensive oral drugs, Premier says, which means their manufacturing is “far less complicated” than for other drugs. To offer immediate help, Premier notes, drug makers such as Teva and Bayer have announced they will donate millions of tablets of the drugs to hospitals or the federal government for further testing.

Owing to “extraordinary public interest” in the off-label use of these drugs, numerous state boards of pharmacy have enacted emergency restrictions on the inappropriate dispensing of chloroquine and hydroxychloroquine, says the Quinism Foundation, a nonprofit organization that supports education and research on medical conditions caused by chloroquine and related drugs. And because of the very real potential for substitution of more dangerous quinolines (such as mefloquine) in place of chloroquine and hydroxychloroquine, the foundation recently called on state boards of pharmacy to enact uniform restrictions on the dispensing of all quinoline antimalarial drugs, with the understanding that any emergency use of any of these medications for public health purposes as attempted pandemic countermeasures would be best coordinated nationally through distribution from the Strategic National Stockpile.

In the meantime, research into hydroxychloroquine’s effectiveness is ongoing. “Coming at it from every angle”—that’s how Terry Welch, spokesman for the Walter Reed Army Institute of Research told Task & Purpose the Army is “leveraging specific competencies” to attack the COVID-19 problem. Among other things, WRAIR’s Emerging Infectious Diseases Branch (EIDB) is working to develop a vaccine against COVID-19 infection, including several versions of a novel vaccine candidate that has been tested in humans. WRAIR has also been conducting research into novel treatments, such as drug candidates similar to those successfully developed to treat malaria, and monoclonal antibodies.

WRAI was able to start its anti-COVID-19 research in early January—directly on the heels of the first reported cases of infection—because of the Institute’s history of researching related viruses. “If we hadn’t done that, we’d be weeks behind,” said Dr. Kayvon Modjarrad, director of EIDB.

The National Institutes of Health (NIH) has also begun a clinical trial, the Outcomes Related to COVID-19 treated with hydroxychloroquine among in-patients with symptomatic Diseases (ORCHID) study. The study will enroll more than 500 adults who are hospitalized with COVID-19 or in an emergency department awaiting hospitalization. All patients will continue to receive clinical care; some will be randomly assigned to also receive hydroxychloroquine. The first participants have been enrolled at Vanderbilt University Medical Center, in Nashville, one of the centers in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network.

In the “urgent race to find effective therapies,” NIH also launched the first clinical trial in the US to evaluate remdesivir, a broad-spectrum antiviral, as a potential treatment for COVID-19.  The trial, which started March 6 at the University of Nebraska Medical Center, is expected to conclude in May. Clinical trials of remdesivir have been ongoing in China, where the virus originated. The NIH study “takes into account” those trial designs. 

Many US hospitals are already using hydroxychloroquine as first-line therapy for COVID-19 patients, despite the lack of supportive clinical evidence. Wesley Self, MD, MPH, lead investigator in the ORCHID trial, says “[D]ata on hydroxychloroquine for the treatment of COVID-19 are urgently needed to inform clinical practice.”

Not only research is needed, but clear expression of the facts about the drugs. In March, shortly after the president began lauding hydroxychloroquine, a Phoenix man died of cardiac arrest and his wife ended up in critical care after they misguidedly ingested chloroquine phosphate, a chemical used to clean fish tanks.  “[W]e understand that people are trying to find new ways to prevent or treat this virus,” said Dr. Daniel Brooks, medical director of the Banner Poison and Drug Information Center in Phoenix, “but self-medicating is not the way to do so.”

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and one of the main spokespersons for science in the hydroxychloroquine debate, has continued to try to make his concerns clear: “I think we’ve got to be careful that we don’t make that majestic leap to assume this is a knockout drug,” he said in late March. “We still need to do the kinds of studies that definitively prove whether any intervention—not just this one, any intervention—is truly safe and effective.”

Hydroxychloroquine, which has been touted without definitive scientific support as a treatment for COVID-19 infection, has special significance for the millions of US military service members and veterans who served in Southwest Asia and other countries with endemic malaria: It’s a critical antimalarial drugs. It’s also needed for US Department of Veterans Affairs (VA) patients with rheumatoid arthritis.

On March 24, the VA Inspector General (IG) surveyed VA medical facilities to determine shortages in equipment as well as “antibiotics, sedatives, pain, and antiviral medications,” although there no known effective treatments for COVID-19. The OIG reported that 12 facilities indicated that they anticipated a shortage of medications, including hydroxychloroquine, lopinavir/ritonavir, IV immunoglobulin, and nebulizer products in the next 14 to 28 days. Facilities in West Haven, CT; Martinsburg, WV; Baltimore, MD; Washington, DC; Durham, NC; Columbia, SC; Tampa, FL; Detroit, MI; Temple, TX; Oklahoma City, OK; Aurora, CO; Seattle, WA; and Phoenix, AZ, all indicated anticipated shortages. At least one facility explicitly worried about access to medications and supplies produced in China and concern about disrupted supply chains may have concerned other facilities as well.

Nevertheless, hydroxychloroquine was at the top of mind both OIG inspectors as well as Veterans Health Administration (VHA) officials. In a formal response to the OIG survey, the VHA asserted: “We object to OIG’s assertions that a 14-day supply of chloroquine or hydroxychloroquine would have any merit. This is both inaccurate and irresponsible. There are active investigations into these drugs and many others, as discussed by Dr. Anthony Fauci. Yet no conclusions have been made on their effectiveness. To insist that a 14 days’ supply of these drugs is appropriate or not appropriate displays this dangerous lack of expertise on COVID-19 and Pandemic response.”

Hydroxychloroquine has been associated with serious adverse effects, such as cardiac arrhythmias and hypoglycemia, and its use against COVID-19 is based, so far, on thin evidence. It has shown promise in a laboratory setting against SARS-CoV-2, the virus that causes COVID-19, and in small studies with patients. Nonetheless, the Food and Drug Administration (FDA) has granted limited emergency authorization for certain uses of chloroquine and hydroxychloroquine against COVID-19. The rapid approval came apparently at the behest of the White House.

Former FDA leaders say the authorization has jeopardized research to learn the drugs’ real value in pandemic patients. They also charge that the decision undermines FDA’s scientific authority because it appears to be reacting to political advocacy. 

Despite the concerns, a run on chloroquine and hydroxychloroquine has been underway. According to a March 20 blog post by Premier, a hospital purchasing organization, orders for chloroquine and hydroxychloroquine jumped “dramatically” between March 1 and March 17, by 3,000% and 260%, respectively. Fortunately, these are older, relatively inexpensive oral drugs, Premier says, which means their manufacturing is “far less complicated” than for other drugs. To offer immediate help, Premier notes, drug makers such as Teva and Bayer have announced they will donate millions of tablets of the drugs to hospitals or the federal government for further testing.

Owing to “extraordinary public interest” in the off-label use of these drugs, numerous state boards of pharmacy have enacted emergency restrictions on the inappropriate dispensing of chloroquine and hydroxychloroquine, says the Quinism Foundation, a nonprofit organization that supports education and research on medical conditions caused by chloroquine and related drugs. And because of the very real potential for substitution of more dangerous quinolines (such as mefloquine) in place of chloroquine and hydroxychloroquine, the foundation recently called on state boards of pharmacy to enact uniform restrictions on the dispensing of all quinoline antimalarial drugs, with the understanding that any emergency use of any of these medications for public health purposes as attempted pandemic countermeasures would be best coordinated nationally through distribution from the Strategic National Stockpile.

In the meantime, research into hydroxychloroquine’s effectiveness is ongoing. “Coming at it from every angle”—that’s how Terry Welch, spokesman for the Walter Reed Army Institute of Research told Task & Purpose the Army is “leveraging specific competencies” to attack the COVID-19 problem. Among other things, WRAIR’s Emerging Infectious Diseases Branch (EIDB) is working to develop a vaccine against COVID-19 infection, including several versions of a novel vaccine candidate that has been tested in humans. WRAIR has also been conducting research into novel treatments, such as drug candidates similar to those successfully developed to treat malaria, and monoclonal antibodies.

WRAI was able to start its anti-COVID-19 research in early January—directly on the heels of the first reported cases of infection—because of the Institute’s history of researching related viruses. “If we hadn’t done that, we’d be weeks behind,” said Dr. Kayvon Modjarrad, director of EIDB.

The National Institutes of Health (NIH) has also begun a clinical trial, the Outcomes Related to COVID-19 treated with hydroxychloroquine among in-patients with symptomatic Diseases (ORCHID) study. The study will enroll more than 500 adults who are hospitalized with COVID-19 or in an emergency department awaiting hospitalization. All patients will continue to receive clinical care; some will be randomly assigned to also receive hydroxychloroquine. The first participants have been enrolled at Vanderbilt University Medical Center, in Nashville, one of the centers in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network.

In the “urgent race to find effective therapies,” NIH also launched the first clinical trial in the US to evaluate remdesivir, a broad-spectrum antiviral, as a potential treatment for COVID-19.  The trial, which started March 6 at the University of Nebraska Medical Center, is expected to conclude in May. Clinical trials of remdesivir have been ongoing in China, where the virus originated. The NIH study “takes into account” those trial designs. 

Many US hospitals are already using hydroxychloroquine as first-line therapy for COVID-19 patients, despite the lack of supportive clinical evidence. Wesley Self, MD, MPH, lead investigator in the ORCHID trial, says “[D]ata on hydroxychloroquine for the treatment of COVID-19 are urgently needed to inform clinical practice.”

Not only research is needed, but clear expression of the facts about the drugs. In March, shortly after the president began lauding hydroxychloroquine, a Phoenix man died of cardiac arrest and his wife ended up in critical care after they misguidedly ingested chloroquine phosphate, a chemical used to clean fish tanks.  “[W]e understand that people are trying to find new ways to prevent or treat this virus,” said Dr. Daniel Brooks, medical director of the Banner Poison and Drug Information Center in Phoenix, “but self-medicating is not the way to do so.”

Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, and one of the main spokespersons for science in the hydroxychloroquine debate, has continued to try to make his concerns clear: “I think we’ve got to be careful that we don’t make that majestic leap to assume this is a knockout drug,” he said in late March. “We still need to do the kinds of studies that definitively prove whether any intervention—not just this one, any intervention—is truly safe and effective.”